Naive Patients Research Articles

CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line

BackgroundImmune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers.MethodsThe levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients).ResultsIn both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors.ConclusionHigh levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.

Myeloid-T cell interplay and cell state transitions associated with checkpoint inhibitor response in melanoma.

The treatment of melanoma, the deadliest form of skin cancer, has greatly benefited from immunotherapy. However, many patients do not show a durable response, which is only partially explained by known resistance mechanisms. We performed single-cell RNA sequencing of tumor immune infiltrates and matched peripheral blood mononuclear cells of 22 checkpoint inhibitor (CPI)-naive stage III-IV metastatic melanoma patients. After sample collection, the same patients received CPI treatment, and their response was assessed. CPI responders showed high levels of classical monocytes in peripheral blood, which preferentially transitioned toward CXCL9-expressingmacrophages in tumors. Trajectories of tumor-infiltrating CD8+ Tcells diverged at the level of effector memory/stem-like Tcells, with non-responder cells progressing into a state characterized by cellular stress and apoptosis-related gene expression. Consistently, predicted non-responder-enriched myeloid-T/natural killer cell interactions were primarily immunosuppressive, while responder-enriched interactions were supportive of Tcell priming and effector function. Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response. This research was funded by Roche Pharma Research and Early Development.

Abstract 5895: N17350 kills cancer cells, spares immune cells, and regresses CDX tumors from chemotherapy naive and experienced patients

Abstract Background. While multiple studies have demonstrated improved clinical outcomes in patients receiving concurrent chemotherapy and immunotherapy, clinical synergy may be limited by the destructive effects of DNA-damaging chemotherapy on non-cancer cells, including key constituents of anti-tumor immunity (e.g. mature T cells). Furthermore, when first-line chemotherapy fails, subsequent lines of chemotherapy produce lower response rates. Thus, new approaches that eradicate cancer cells while preserving immune cells may be required to more efficiently induce anti-tumor immunity as monotherapy or in combination with immunotherapy. Neutrophil elastase (ELANE), a neutrophil-derived serine protease, kills a wide range of cancer cells without harming immune cells through a unique mechanism involving histone H1 and the death domain of CD95. Here, we compared N17350, an optimized biologic leveraging the ELANE pathway, and chemotherapies for their ability to kill cancer cells and preserve immune cells from primary tumors of ovarian cancer (OvCa) patients and evaluated efficacy in OvCa patient cell-derived xenografts (CDXs) and a 4T1 model of metastatic breast cancer. Methods. For in vitro studies, cancer cells and CD45+ immune cells were isolated from primary tumors of chemotherapy naïve and experienced OvCa patients. Cells were treated with N17350, oxaliplatin, or doxorubicin 24h post-isolation, and viability was quantified by calcein-AM. For in vivo studies, primary OvCa cells were injected into nude mice to create CDX models. Mice were treated with 2 doses of N17350 (400μg/100mm3, intratumoral) or carboplatin (100mg/kg, intraperitoneal), and effects on tumor growth were quantified. In 4T1 model, N17350 was compared to oxaliplatin, alone or in combination with anti-CTLA4, and effects on tumor growth and immune profile were assessed. Results. N17350 killed primary cancer cells from all OvCa patients tested but was well tolerated by CD45+ tumor immune cells from the same patients. In contrast, doxorubicin and oxaliplatin showed similar toxicity to both cell types. N17350 killed cancer cells from chemotherapy naïve and experienced patients with equal efficacy, while doxorubicin and oxaliplatin showed less efficacy in patients previously treated with chemotherapy. N17350 rapidly regressed tumors in all OvCa CDX models and exhibited markedly improved efficacy over carboplatin. In the 4T1 model, N17350 outperformed oxaliplatin in terms of regressing tumors, elevating tumor immune cells, and combining with anti-CTLA4. Conclusions. Our data demonstrate that N17350 kills OvCa tumors in vitro and in vivo while sparing CD45+ immune cells in both chemotherapy naïve and experienced patients. Together with previous data showing that N17350 induces immunogenic tumor cell death, these findings suggest that N17350 could improve clinical outcomes compared to chemoimmunotherapy. Citation Format: Chang Cui, Ravindra Gujar, Christine Lee, Maria Fumagalli, Nicole Martinez, Hannah Liu, Nicole Grigaitis, Sonia Feau, Afshin Bahador, Alain P. Algazi, Lev Becker. N17350 kills cancer cells, spares immune cells, and regresses CDX tumors from chemotherapy naive and experienced patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5895.

Molecular Epidemiology of HIV-1 Subtypes and Primary Antiretroviral Resistance Profiles in Northern Cyprus: First Data Series.

The distribution of human immunodeficiency virus-1 (HIV-1) subtypes indicates difference from region to region and in risk groups acquiring the disease worldwide. Although subtype C is more in terms of total cases, subtype B is dominant in certain regions, especially in western and central Europe. Molecular epidemiological studies are essential for the control, effective treatment, and understanding in transmission routes of HIV-1 infection. This study aims to determine the molecular epidemiology and antiretroviral drug resistance profiles of HIV-1 in northern Cyprus. The study involved 71 naive HIV-positive patients diagnosed in northern Cyprus between 2016 and 2022. HIV-1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis (neighbor-joining method) of pol gene sequences. Drug resistance mutations were analyzed using the World Health Organization (WHO) lists of mutations for surveillance. The Stanford University HIVdb program was used to interpret drug resistance mutations. In our study, 40 of 71 samples were successfully sequenced. Subtype B of HIV-1 was dominant with a rate of 52.5%, followed by CRF02_AG (20%) and G (7.5%) subtypes. The rate of subtype B (71.4%) in northern Cyprus was significantly higher than in the other country of origin (p = .028). Antiretroviral drug resistance was found in 15% of the sequenced serum samples. Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside nucleotide reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) resistance rates were 10% (4/40), 7.5% (3/40), and 2.5% (1/40), respectively. According to the results, it is noteworthy that the dominant subtype circulating in northern Cyprus is the B subtype, and CRFs were detected at a higher rate than expected.

A Predictive Model of the HIV Infection Course

The course of HIV infection depends on the degree of HIV suppression during ART.The objective: to evaluate feasibility of using three factors: viral load (VL), HIV reservoir and CD8 T cells before ART initiation to estimate future levels of “residual” viremia and develop a predictive model.Subjects and Methods. 74 naive patients with HIV infection were enrolled in the study. The HIV reservoir, VL and CD4, CD8 counts were tested before ART initiation and then every 6 months. The patients were followed up for 12 months. Discriminant analysis was used.Results. After 12 months of ART, 69/74 (93.2%) patients had undetectable VL including 14 patients with residual viremia (RV) and 55 in whom no virus was detected. The probability of persisting RV after 12 months of ART was assessed first by one factor – VL prior to ART, after that by three factors – VL, HIV reservoir (HIV DNA), CD8 count prior to ART. A predictive model formula was generated using those factors: D = -5.288-0.001 CD8+1.342VL+0.08 HIV DNA. With discriminant function D>0.065, the patient has a high probability of RV after 12 months of ART; with D ≤0.065, the probability of RV is low. This prognosis should be taken into account when choosing an ART regimen ensuring its maximum optimization.

Single Center Evaluation of Long-Term Results of Glargin U-300 in Insulin Naive Patients In a Real-World Setting

Objective: Insulin therapy stands as one of the most effective and well-established therapeutic options for managing glycemic control in Diabetes Mellitus (DM). Glargine 300 U/mL (Gla-300) represents a new long-acting insulin analog, which has demonstrated a decrease in the risk of hypoglycemia and a reduction in the total number of injections due to prolonged insulin absorption. In this study, we investigated the long-term effects of Gla-300 on Fasting Plasma Glucose (FPG) and HbA1c levels, as well as the incidence of hypoglycemia in insulin-naive patients admitted to the Internal Medicine outpatient clinic, over a period of 0, 3, 6, 12, and 24 months.. Material and Methods: Between January 2018 and June 2022, insulin-naive patients diagnosed with Type 2 Diabetes Mellitus (T2DM) who initiated treatment with Gla-300 and sought care at the Internal Medicine outpatient clinic were subjected to retrospective analysis. Results: The study included 49 insulin-naive patients. A statistically significant decrease was observed in Fasting Plasma Glucose (FPG) (p = 0.03) and HbA1c (p = 0.02) levels during the 24-month follow-up period of Glargine U-300. Additionally, a significant reduction in both FPG (p < 0.01) and HbA1c (p < 0.01) values was achieved at the time of diagnosis and at 3 months. Hypoglycemia was reported in only 1 patient (2%) during our study, indicating a very low hypoglycemia rate. Conclusion: Diabetes mellitus (DM) poses a significant public health challenge, resulting in economic burden and diminished quality of life. Developed to address these challenges, Gla-300 serves as a long-acting basal insulin that effectively reduces the risk of hypoglycemia while offering targeted glycemic control, as evidenced by our study findings. In Turkey, there is a pressing need for multicenter, prospective real-world studies that incorporate parameters such as insulin dosage and weight monitoring.

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated. To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls. In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022. Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included. Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias. The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability. Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92). Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

Glucocorticoid use in psoriatic arthritis and treatment outcomes: does the gender have a role?

BackgroundSystemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA).ResultsFifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed.ConclusionSystemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis.

Leprosy in North India in Post-Elimination Era: A Retrospective Study

Abstract Background: India achieved elimination target for leprosy in December 2005. However, many pockets in the country continue to report significant number of cases. Aim: The aim of the study was to study the profile of leprosy cases presenting to a tertiary care hospital in North India in post-elimination era. Patients and Methods: The study was conducted at Hansen’s disease clinic. The study design was a retrospective observational study. Chart review of treatment naive leprosy patients enrolled between 1st January 2018 and 31st December 2019 was done. Data regarding demographic profile, clinical spectrum of leprosy, slit-skin smears (SSSs) and histopathological findings were analysed. Statistical Analysis: Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 23 (SPSS Inc., Chicago, IL, USA). Data were statistically described in terms of range, mean ± standard deviation, frequency (number of cases), and relative frequency (percentages). Results: Amongst a total of 115 patients, males (68%, n = 79/115) outnumbered females. Children (<15 years) constituted 0.86% cases (n = 1/115) and 26% cases (n = 30/115) were above 50 years of age. Multibacillary leprosy (73%, n = 84/115) was more common. Borderline lepromatous (41.7%, n = 48/115) was the most common clinical type of leprosy, whereas Grade 2 disability was noted amongst 0.05% (n = 6/115) patients at presentation. SSS were positive in 60% (69/115) cases. Conclusions: The present study showed a significant increase in cases in the older age group and decrease in new cases in children. Furthermore, multibacillary cases outnumbered the paucibacillary cases. Similar trends were reported to be an indicator of decreasing incidence of leprosy in countries that eliminated leprosy. We speculate that India may be entering a phase of decreased community transmission of leprosy. Further, multicentric studies across the country may throw more light.

Sex difference in association between suicide attempts and lipid profile in first-episode and drug naive patients with major depressive disorder

BackgroundThe relationship between suicide attempts and lipid profiles in patients with major depressive disorder (MDD) remains uncertain. The purpose of this study was to investigate sex differences in the relationship between suicide attempts and plasma lipid profiles in a large sample of first-episode and drug naive (FEDN) MDD patients. MethodsWe recruited 1718 FEDN MDD patients and gathered demographic, clinical, and blood lipid data. The Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and the Positive and Negative Syndrome Scale were used to assess the symptoms of patients. ResultsThere was no significant difference in the prevalence of suicide attempts between male and female MDD patients. The suicide attempt group had higher levels of depression, anxiety, psychotic symptoms, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), but lower levels of high-density lipoprotein cholesterol (HDL-C) levels than the non-suicide attempt group. Binary logistic regression showed that TC levels were significantly correlated with suicidal attempts in both male and female patients. Correlation analysis revealed that the levels of TC, HDL-C and LDL-C were significantly associated with the number of suicide attempts in both male and female patients. Further multiple linear regression revealed that TC levels were significantly associated with the number of suicide attempts in male patients only. ConclusionsLipid biomarkers, particularly high TC levels, are associated with suicide attempts in both male and female MDD patients. However, there is gender difference in association between lipid biomarkers, especially TC levels, and the number of suicide attempts in MDD patients.

Biosimilar perceptions among autoimmune prescribers and pharmacists in health system specialty pharmacy.

By the end of 2023, 10 self-administered biosimilars indicated for autoimmune conditions are expected to launch in the United States, resulting in alternative treatment options for patients and a potential for cost savings. However, studies about perception and knowledge of self-administered biosimilars among health system prescribers and health system specialty pharmacists are limited. To assesses knowledge and perceptions of biosimilars among autoimmune prescribers and health system specialty pharmacists across the United States. An anonymous, cross-sectional self-administered online questionnaire was conducted among prescribers and health system specialty pharmacists practicing in the specialties of rheumatology, dermatology, and gastroenterology across the United States. The survey was available from January 2023 to February 2023. 31 prescribers and 44 pharmacists completed the questionnaire. Only 16.0% of prescribers and 13.4% of pharmacists reported being "very prepared" to have conversations with patients about biosimilar options. 43% of prescribers indicated they would prescribe a biosimilar to biologic naive patients. However, 13.3% of prescribers would be willing to prescribe a biosimilar to patients successfully established on biologic therapy. Among pharmacists, 68.1% were comfortable recommending a biosimilar substitution to a biologic naive patient, but only 18.1% would recommend a biosimilar substitution to an existing patient successfully established on a biologic therapy. Less than half of prescribers (48.0%) and pharmacists (42.0%) understood regulations of interchangeability and substitution. Our study highlights several knowledge gaps and hesitancies that exist among health system specialty prescribers and pharmacists regarding biosimilar products. Education efforts are needed to overcome the lack of biosimilar adoption, which will increase affordability of therapy for patients and health care savings.

Abstract WP166: Bleeding Risks Among Hemorrhagic Stroke Patients Started on Serotonergic Antidepressants During Subacute Recovery

Background: Early initiation of antidepressants (ADs) are associated with improved functional recovery, but are associated with an increased risk of major bleeds among hemorrhagic stroke (HS) patients. Our objectives were to determine if increased bleeding risk remained if ADs were initiated during subacute recovery and if bleed risks were comparable between AD classes. Methods: A cohort of AD naive first time HS patients (ICD-10 codes 160-162) were identified from Electronic Medical Records of 70 large healthcare organizations (2003-2023). Patients without AD use were considered “No AD” whereas patients started on ADs during subacute recovery (i.e., at least 3 months after the indexed HS) were grouped as Selective Serotonin/Serotonin & Norepinephrine Reuptake Inhibitors (SSRI/SNRI) or “Other AD” (i.e., Mirtazapine, bupropion, trazodone, or tricyclic ADs). Baseline differences were adjusted for using 1:1 matched propensity score (PS). Outcomes included the 1-year risk of a major bleeding event (e.g., gastrointestinal/intracranial bleed or shock), recurrent HS, fall, ischemic stroke (IS) and death Results: The cohort consisted of n=257,595 patients split into 3 groups: No AD (n=250,103), SSRI/SNRI (n=4,180) or Other AD (n=3,312). Matching resulted in good covariate balance for both the SSRI/SNRI vs. No AD (n=8,250 patients) and Other AD vs. SSRI/SNRI (n=6,380 patients) comparisons. SSRI/SNRIs (vs. No AD) were associated with a 33% increase in the risk of a major bleed (RR: 1.33, 95%CI: 1.22-1.45) and significantly higher risks of recurrent HS, fall, IS and death. There were no significant differences in adverse outcomes between AD classes. Discussion: Increased risk of major bleeds and recurrent HS remains if ADs are started during subacute recovery, a time period which aligns with community-based recovery. Our findings may inform care practices of primary care providers and rehabilitation professionals to decrease preventable adverse outcomes.

Durvalumab and guadecitabine in advanced clear cell renal cell carcinoma: results from the phase Ib/II study BTCRC-GU16-043

Epigenetic modulation is well established in hematologic malignancies but to a lesser degree in solid tumors. Here we report the results of a phase Ib/II study of guadecitabine and durvalumab in advanced clear cell renal cell carcinoma (ccRCC; NCT03308396). Patients received guadecitabine (starting at 60 mg/m2 subcutaneously on days 1-5 with de-escalation to 45 mg/m2 in case of dose limiting toxicity) with durvalumab (1500 mg intravenously on day 8). The study enrolled 57 patients, 6 in phase Ib with safety being the primary objective and 51in phase II, comprising 2 cohorts: 36 patients in Cohort 1 were treatment naive to checkpoint inhibitors (CPI) with 0-1 prior therapies and 15 patients in Cohort 2 were treated with up to two prior systemic therapies including one CPI. The combination of guadecitabine 45 mg/m2 with durvalumab 1500 mg was deemed safe. The primary objective of overall response rate (ORR) in cohort 1 was 22%. Sixteen patients (44%) experienced stable disease (SD). Secondary objectives included overall survival (OS), duration of response, progression-free survival (PFS), clinical benefit rate, and safety as well as ORR for Cohort 2. Median PFS for cohort 1 and cohort 2 were 14.26 and 3.91 months respectively. Median OS was not reached. In cohort 2, one patient achieved a partial response and 60% achieved SD. Asymptomatic neutropenia was the most common adverse event. Even though the trial did not meet the primary objective in cohort 1, the tolerability and PFS signal in CPI naive patients are worth further investigation.

Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC.

Phase 1b/2 study of combination ¹⁷⁷Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC.

Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis

ObjectivesLong-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify...

Open Label, Single Centre Study of Babao Relief Capsule as an Adjuvant to HAART in Antiretroviral Naive HIV Patients

HIV continues to be a major global public health issue, having claimed 36.3 million [27.2–47.8 million] lives so far (WHO, 2021). Sub-Sahara Africa remains the far worst affected region, with 20.6 million [16.8 million– 24.4 million] people living with HIV at the end of 2010, compared to 24.4 (22.5-27.3 million) in 2020. Complementary and alternative therapy (CAM) has been used to treat HIV patients by clinicians in conventional health services in combination with highly active antiretroviral therapy (HAART). To determine efficacy of Babao relief capsule when used as an adjuvant to standard HAART in antiretroviral naïve HIV patients. The product is a biological Chinese medicinal preparation, made of herbs. Ingredients include ginseng, beer antler, musk, bezoar, fleeceflower, Chinese angelica, lyceum, pericarpium citri reticulatae, safflower and ophiopogn japonicus. Open Label Phase 1 bridging Clinical trial to study the efficacy of Babao relief capsule when used in combination standard HAART in antiretroviral naïve HIV patients. A total of one hundred and ninety-six (196) adult patients attending the HIV clinic were randomly selected. The interventional group was on Babao relief capsule and HAART while the control group was on HAART only. The study shows general efficacy of the standard HAART drugs. However, the interventional arm showed a significant increase in the CD4 cell count, showing that BRC had booster effects in the efficacy of HAART. Keywords: HIV, Complementary and alternative therapy, Babao relief capsule, standard highly active antiretroviral therapy.

Tenofovir Alafenamide in the Treatment of Naïve Chronic Hepatitis B: A Single-Centre Retrospective Study

Chronic hepatitis B (CHB) is a major global health problem affecting approximately 257 million people worldwide. Tenofovir alafenamide (TAF) is a new, effective antiviral drug for chronic hepatitis B. However, real-world data on the efficacy of TAF in treating naive patients are limited. This study aimed to evaluate TAF's efficacy in treating naive CHB patients. Factors associated with virological response and alanine aminotransferase (ALT) normalization were also analyzed in the study. The study included 41 treatment-naive CHB patients who started TAF between January 2021 and December 2022. Demographic, clinical, and laboratory data were collected at baseline and week 48. The primary endpoints were complete virologic response (CVR) and ALT normalization at week 48. At week 48, ALT and hepatitis B virus-deoxyribonucleic acid (HBV DNA) levels decreased to statistically significant levels (both p

Relationships between Patient-Reported Outcome Measures and Clinical Measures in Naïve Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Ranibizumab.

Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.

P675 Comparative efficacy of Infliximab, Adalimumab, and Ustekinumab in patients with biologics naive Crohn's disease：a retrospective observational single-center study

Abstract Background The number of biologics available for Crohn's disease (CD) has increased dramatically, but there is no established standard of selection and few direct comparisons of efficacy among the agents. In this study, we compared the efficacy of infliximab (IFX), adalimumab (ADA), and ustekinumab (UST) in biologics naive CD patients. Methods A retrospective analysis of clinical data from CD patients who received IFX, ADA, and UST as 1st biologics during the period 2014-2023 was performed. Results Of 137 CD patients, 8 patients who received IFX, 17 patients who received ADA, and 10 patients who received UST as 1st biologics were included. Patient background (IFX/ADA/UST group) was as follows: median age was 32/21/22 years, median disease duration was 1/2/2 years, median HBI was 5/6/6, median SES-CD was 9/6/9, median CRP was 1.59/0.49/1.03 mg/dl, median albumin was 3.7/4.3/4.2 g /dl. Prednisolone or budesonide was concomitantly administered at induction in 5 (62.5%)/4 (23.5%)/0 (0%) patients.The cumulative remission rate (IFX/ADA/UST group) was 62.5%/58.8%/85.7% at 52 weeks after biologics induction in all patients, with a higher rate in the UST group. The steroid-free remission rates at 52 weeks (IFX/ADA/UST group) were 50.0%/58.8%/90.0%, which were higher in the UST group. For patients with HBI≥5 at the biologics induction, the remission rate after 8/16 weeks was 83.3% (5/6)/66.7% (4/6) in the IFX group, 54.5% (6/11)/63.6% (7/11) in the ADA group and 75.0% (6/8)/100% (8/8) in the UST group. There were no significant differences among all groups. Regarding adverse events, one case of skin rash and one case of dizziness were observed in the IFX group, one case of skin rash was observed in the ADA group, and no adverse event was observed in the UST group. One case of intestinal obstruction occurred in the IFX group and two cases in the ADA group, but not in the UST group. Conclusion Induction of UST in biologics naive CD patients may be as effective as anti-TNFα antibodies.

P879 Comparative Efficacy of Biologics and Small Molecule Therapies for the Induction and Maintenance of Endoscopic and Histological Remission in Ulcerative Colitis: A Systematic Review and Network Meta-analysis

Abstract Background Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but lack of comparative efficacy trials make treatment choices a clinical challenge. We aimed to compare the relative efficacy of biologics and small molecules in achieving endoscopic and histological remission in patients with moderate to severe UC. Methods The literature was searched between January 1990 and July 2023. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included to assess the efficacy of biologics or small molecule drugs as induction or maintenance therapies for patients with UC. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score ≤1), whereas secondary outcomes were the induction and maintenance of endoscopic (Mayo endoscopic score = 0) and histological remission. Sub-analysis was performed based on previous exposure to biologic therapy. We used a random effects model and reported data as odd ratio (OR) with 95% confidence intervals (CIs). Results We identified 34 studies that met our inclusion criteria, with a total of 12,227 patients with UC. Upadacitinib was superior to most biologics in inducing endoscopic improvement and remission as well as maintaining endoscopic improvement and histological remission. Etrasimod ranked second, after upadacitinib, in maintenance of endoscopic improvement in both biologic naive (80.4%) and experienced (78.9%) patients. Infliximab was superior to adalimumab (OR 1.88, 95% CI, 1.07; 3.29) and vedolizumab (OR1.85, 95% CI, 1.13; 3.03) in inducing endoscopic improvement in overall UC patients. Filgotinib 200 mg (OR 4.76, 95% CI, 1.89; 5.88) and vedolizumab (OR 4.16, 95% CI, 2.94; 6.25) were superior to adalimumab in maintaining histological remission. In biologic naive patients, infliximab was found to be superior to adalimumab (OR 1.80, 95% CI, 1.05;3.07), vedolizumab (OR 5.20, 95% CI, 2.04;7.69), and golimumab (OR 6.30, 95% CI, 3.39;9.71) in inducing endoscopic improvement Conclusion Upadacitinib appears to be superior to other therapies in achieving both endoscopic improvement and remission as well as maintaining histological remission. Furthermore, etrasimod, filgotinib and tofacitinib ranked high in achieving these outcomes. This study highlights the role of small molecules drugs as effective alternatives to biologics.